EXPLORING THE POTENTIAL OF OPTIMISED STARCH PARTICULATES AS PLATFORM FOR ORAL DELIVERY OF A MODEL GASTROLABILE DRUG CEFOTAXIME
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Date
2009
Authors
BUKHARI, NADEEM IRFAN
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Abstract
Use of particulates is a prominent approach for engineering delivery systems to
overcome gastrointestinal barriers. Starch has desired properties necessary for a particulate
fabrication material. It is biodegradable, safe, cheap and abundant however, has attracted less
research attention, comparative to other biopolymers. This work reports simple and
innovative top-down physical methods including spray-drying, ultrasonication and
nanomilling for production of micron and submicron size starch particles. The optimised
starch particulates were fabricated with use of processing and formulative aids employing
computer-aided algorithm.
Ultrasonication was unsuccessful in generating reproducible starch particles with
processing aids used. Spray-drying produced particle size of 21.64 ± 1.36 ).tm (dispersion in
uniformity of particle size 0.56 ± 0.135) for com starch. Nanomilling seemed promising for
production of reproducible submicron particles with control over particle characteristics by
modulation of process and formulative parameters. Potato starch produced cross-linked
particles with size and polydispersity (PDI) of 200 nm and 0.25, respectively. The zeta
potential of potato starch was> -21 mY. Uncross-linked soluble starch yielded cationic,
anionic and neutral particles with charges +8.59 ± 0.45, -10.50 ± 0.20 and 2.00 ± 0.30 mY,
respectively with particle size < 200 nm and PDI < 0.25. Com starch uncross-linked particle
size was around 500 nm with PDI > 0.40 which was slightly higher than generally accepted
PDI values, thus com starch particles were not optimised. Cross-linked potato and com
starch were somewhat hydrophobic.
The spray-dried com starch, nanomilled cross- and uncross-linked potato starch and
anionic, cationic and neutral soluble starch were selected for in vitro and in vivo studies.
'< Potato and soluble starch demonstrated loading efficiency> 9.55 %. Com starch showed low
t
loading efficiency of 2.30 %., probably due to its lower yield (27.77 ± 1.48 %) as compared
to that of potato and com starch (> 84 %). Particle size growth was observed over time
prominently, in soluble starch particulates. The in vitro release of particulates followed zero
order model with diffusion exponent < 1, characterising release by swelling-diffusion.
Comparative to free cefotaxime sodium, the uncross-linked potato starch and cationic
soluble starch showed 5.28 and 3.11 folds increase in bioavailability, respectively. Thus,
starch may have potential to deliver gastrolabile drug, cefotaxime sodium and thereby, to
enhance its oral bioavailability.
In conclusion, the micron and submicron size optimised starch particles can be
prepared using physical methods by blending pharmaceutical science with computer-aided
optimisation. The particulates are capable to enhance bioavailability of cefotaxime sodium.
However, physical stability of particulates is needed to be improved further.
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Keywords
GASTROLABILE , DRUG CEFOTAXIME